Comparative Effects of P2Y12 Inhibitors on Thrombus Biology and Inflammatory Responses in Atherothrombotic Cardiovascular Disease: A Systematic Review of Randomized Controlled Trials

This systematic review investigates the biological impact of various P2Y12 receptor inhibitors on thrombus composition and inflammatory activity in patients with acute coronary syndromes undergoing percutaneous coronary intervention (PCI). A comprehensive literature search across four major databases identified four randomized controlled trials that met the inclusion criteria for evidence synthesis. These trials examined ticagrelor, prasugrel, cangrelor, and genotype-guided strategies in comparison to clopidogrel, assessing outcomes such as inflammatory cell infiltration, platelet reactivity, and myocardial reperfusion parameters. Overall, ticagrelor and prasugrel were associated with more favorable modulation of thromboinflammatory and vascular healing markers compared with clopidogrel; these effects were most evident in studies evaluating neutrophil infiltration, myeloperoxidase activity, and early post-PCI ischemic events. However, variations in study design, endpoints, and follow-up duration limited direct comparisons and precluded definitive conclusions. In addition, one mechanistic study protocol describing the assessment of extracellular vesicle-based biomarkers was identified but excluded from the evidence synthesis due to the absence of outcome data. Collectively, the available evidence provides preliminary mechanistic support for the hypothesis that certain P2Y12 inhibitors may exert anti-inflammatory and thrombus-modifying effects beyond their platelet-inhibiting effects. Larger, standardized, and mechanistically focused trials are warranted to validate these findings and guide precision-based antiplatelet therapy in cardiovascular disease.